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Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions.
Hepokoski, Mark L; Odish, Mazen; Lam, Michael T; Coufal, Nicole G; Rolfsen, Mark L; Shadel, Gerald S; Moyzis, Alexandra G; Sainz, Alva G; Takiar, Puja G; Patel, Sagar; Leonard, Austin J; Samandari, Negin; Hansen, Emily; Trescott, Samantha; Nguyen, Celina; Jepsen, Kristen; Cutter, Gary; Gillespie, Mark N; Spragg, Roger G; Sasik, Roman; Ix, Joachim H.
Afiliación
  • Hepokoski ML; VA San Diego Healthcare System, San Diego, California.
  • Odish M; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.
  • Lam MT; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.
  • Coufal NG; VA San Diego Healthcare System, San Diego, California.
  • Rolfsen ML; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.
  • Shadel GS; Salk Institute for Biological Sciences, La Jolla, California.
  • Moyzis AG; Department of Pediatrics, University of California San Diego, San Diego, California.
  • Sainz AG; Rady Children's Hospital, San Diego, California.
  • Takiar PG; Department of Medicine, School of Medicine, University of California San Diego, San Diego, California.
  • Patel S; Salk Institute for Biological Sciences, La Jolla, California.
  • Leonard AJ; Salk Institute for Biological Sciences, La Jolla, California.
  • Samandari N; Salk Institute for Biological Sciences, La Jolla, California.
  • Hansen E; Department of Pathology, Yale School of Medicine, New Haven, Connecticut.
  • Trescott S; Department of Medicine, School of Medicine, University of California San Diego, San Diego, California.
  • Nguyen C; Division of Pulmonary and Critical Care and Sleep Medicine, University of California San Diego, San Diego, California.
  • Jepsen K; Department of Medicine, School of Medicine, University of California San Diego, San Diego, California.
  • Cutter G; VA San Diego Healthcare System, San Diego, California.
  • Gillespie MN; Department of Pediatrics, University of California San Diego, San Diego, California.
  • Spragg RG; Department of Pediatrics, University of California San Diego, San Diego, California.
  • Sasik R; Department of Pediatrics, University of California San Diego, San Diego, California.
  • Ix JH; Institute for Genomic Medicine, University of California San Diego, La Jolla, California.
Am J Physiol Lung Cell Mol Physiol ; 323(1): L84-L92, 2022 07 01.
Article en En | MEDLINE | ID: mdl-35699291
Increased plasma mitochondrial DNA concentrations are associated with poor outcomes in multiple critical illnesses, including COVID-19. However, current methods of cell-free mitochondrial DNA quantification in plasma are time-consuming and lack reproducibility. Here, we used next-generation sequencing to characterize the size and genome location of circulating mitochondrial DNA in critically ill subjects with COVID-19 to develop a facile and optimal method of quantification by droplet digital PCR. Sequencing revealed a large percentage of small mitochondrial DNA fragments in plasma with wide variability in coverage by genome location. We identified probes for the mitochondrial DNA genes, cytochrome B and NADH dehydrogenase 1, in regions of relatively high coverage that target small sequences potentially missed by other methods. Serial assessments of absolute mitochondrial DNA concentrations were then determined in plasma from 20 critically ill subjects with COVID-19 without a DNA isolation step. Mitochondrial DNA concentrations on the day of enrollment were increased significantly in patients with moderate or severe acute respiratory distress syndrome (ARDS) compared with those with no or mild ARDS. Comparisons of mitochondrial DNA concentrations over time between patients with no/mild ARDS who survived, patients with moderate/severe ARDS who survived, and nonsurvivors showed the highest concentrations in patients with more severe disease. Absolute mitochondrial DNA quantification by droplet digital PCR is time-efficient and reproducible; thus, we provide a valuable tool and rationale for future studies evaluating mitochondrial DNA as a real-time biomarker to guide clinical decision-making in critically ill subjects with COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Dificultad Respiratoria / COVID-19 Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Dificultad Respiratoria / COVID-19 Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Humans Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2022 Tipo del documento: Article Pais de publicación: Estados Unidos